MOTS-c
A mitochondrial-encoded peptide studied for its role in metabolism, exercise capacity, and mitochondrial signaling.
In plain English
MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA. It is the most-studied of a growing family of 'mitochondrial-derived peptides' that appear to act as signals between mitochondria and the rest of the cell. In rodents, MOTS-c improves insulin sensitivity, increases exercise capacity, and reduces age-related declines in metabolic function. Human data are still very early — there are no large RCTs to date — but circulating MOTS-c has been correlated with metabolic health in observational studies. It is not FDA-approved.
What it is
MOTS-c (Mitochondrial Open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene.
Mechanism (summary)
MOTS-c activates AMPK, modulates the folate cycle, and translocates to the nucleus under stress where it regulates transcription of metabolic and stress-response genes.
Why people research it
- Insulin sensitivity and glucose disposal
- Exercise capacity and mitochondrial fitness
- Aging biology and longevity signaling
- Obesity-related metabolic dysfunction
Human evidence
Observational data show lower circulating MOTS-c in conditions of insulin resistance and aging. Direct human interventional trials are not yet published in mainstream RCT form.
Animal / lab evidence
MOTS-c administration in mice improves insulin sensitivity, prevents diet-induced obesity, increases running endurance, and rescues age-related metabolic decline.
Key studies
Each summary explains the design, what was found, and what it doesn't prove.
In mice, MOTS-c kept insulin working better as the animals aged or gained weight.
MOTS-c-treated mice ran longer on a treadmill and showed muscle gene changes that looked like a trained state.
History
Identified by Pinchas Cohen and colleagues at USC in 2015 as the first mitochondrial-encoded peptide with hormone-like activity.
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